Impact of Glucagon-like Peptide-1 Receptor Agonists on Metabolic Health in Liver Transplant Recipients

Abstract

Background. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), initially approved for the management of diabetes, have demonstrated a wide range of metabolic benefits. However, their benefit and safety profile in liver transplant (LT) recipients remain poorly defined. Methods. This study retrospectively analyzed adults who had undergone LT and had concomitant type 2 diabetes mellitus. Thirty-eight post-LT recipients treated with GLP-1RA for type 2 diabetes mellitus were matched with patients treated with insulin therapy 1:1 using propensity scoring for age, sex, ethnicity, cause of cirrhosis, and immunosuppression. This matching aimed to assess the metabolic effects and safety profile of GLP-1RA after LT. Results. The 2 groups were similar at baseline with regard to clinical characteristics, except that time from LT was greater in patients who were on GLP-1RA. Semaglutide was the most commonly used GLP-1RA. LT recipients who received GLP-1RA lost approximately 8% of body weight during 12 mo, whereas patients on insulin therapy gained approximately 10% of body weight during the same period. Patients on GLP-1RA were less likely to have hepatic steatosis compared with patients on insulin therapy post-LT. Both GLP-1 and insulin were well tolerated, with no significant impact on renal function, immunosuppression, or rejection. GLP-1RA was stopped in only 1 patient due to persistent nausea. Conclusions. GLP-1RA therapy is safe after LT and is well tolerated. Aside from glycemic control, metabolic benefits of GLP-1RA included weight loss and lower prevalence of steatosis in LT recipients. The study findings provide much-needed safety data for GLP-1RA in LT patients and foundational data to design prospective trials to evaluate metabolic benefits of GLP-1RA.